The Drosophila embryonic epidermis has been an exemplary model system for understanding how transcription factor networks and cell signaling modules are coordinated to pattern tissues and embryos. Recently, it has begun to reveal how those circuits impact the underlying cell biology to drive morphogenesis. Thus, the study of this epithelium holds the promise of a complete understanding of the circuit between developmental cell signaling and the effector proteins that control cellular morphogenesis. This is the overarching focus of this proposal. The remodeling of cell sheets underlies most of morphogenesis during development. For instance, it is the key to extending the axis of the vertebrate body plan, gastrulation, neurulation, and organ formation, in general. When these processes go awry, severe birth defects can result. Surprisingly, it is not understood how specific cell interfaces are selected out for remodeling. Within cell sheets, individual cells often can discern with high fidelity one of their edges from all others, and this is known as tissue polarity. In fact, tissue polarity is likely what assists in the ability of cells to select out a specific edge for remodeling. Tissue polarity is a conserved feature, operating in most if not all epithelia from the invertebrate, Drosophila, through to mammals, and a similarly conserved set of genes is at the center of assigning that polarity. Still, it is unclear how these genes confer polarity, what the effector mechanisms are, and how the polarity circuit is linked to developmental cell signaling. This proposal focuses on two key aspects of tissue cellular morphogenesis: the remodeling of cell sheets;and the assignment of polarity within the plane of the epithelium (so-called "tissue-polarity"). Finally, this work attempts to identify the cell biological mechanisms at the heart of these rearrangements.

Public Health Relevance

Cell polarity is a driving force that shapes embryos and organ systems. Defects in polarity underlie several syndromes, such as ciliary diseases, and deafness. The genes that coordinate polarity were first identified in Drosophila, and their continued study in fruitflies is necessary to understand how they work.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM045747-21
Application #
8469042
Study Section
Development - 2 Study Section (DEV2)
Program Officer
Hoodbhoy, Tanya
Project Start
1992-01-01
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
21
Fiscal Year
2013
Total Cost
$305,590
Indirect Cost
$104,966
Name
University of Pennsylvania
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Simone, Robert P; DiNardo, Stephen (2010) Actomyosin contractility and Discs large contribute to junctional conversion in guiding cell alignment within the Drosophila embryonic epithelium. Development 137:1385-94
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